The ultimate goal of this project is to develop a hand-held device with a plug-and-play nanosensor platform based on biomolecule-gated nanowire field effect transistor (FET) sensors. The principle of the nanowire FED sensor has been demonstrated by Prof. Charlies Lieber's group at Harvard University. The technology requires no label and combines the specificity of antibody-antigen binding with the exquisitely high sensitivity associated with electrical properties of semiconductor nanowires to achieve near single molecule detection. Our objective in this phase I program is to demonstrate the selectivity and sensitivity of nanowire FET nanosensors for anthrax detection. We will develop chemistry for the immobilization of anti-anthrax antibody on the surface of Si nanowires, establish a process for the fabrication of nanowire FET sensors, optimize electrical signal response of devices upon anthrax maker, protective antigen (PA) binding, and measure the detection limits and dynamic response of the devices at physiologically relevant concentrations.The proposed studies will define fundamental properties of nanowire sensors for selective detection of the biomolecular marker under in-vitro conditions. We believe that these studies will lay the groundwork for developing a very exciting and important program for the NIH. The nanowire nanosensor devices developed in this project will serve as a stepping stone to the creation of minimally-invasive in-vivo sensors for real-time monitoring, and moreover, could be used to develop devices that could simultaneously monitor a large set of protein markers in patients known to be high risk - this could lead to detection at a stage simply not possible today. Lastly, integrated nanosensor arrays could serve as a new tool for discovery and screening in molecular biology with parallelism and sensitivity not possible using any other sensor/detection technology.